Disease modifying anti-rheumatic activity of the alkaloid montanine on experimental arthritis and fibroblast-like synoviocytes

Abstract

Montanine is an alkaloid isolated from Rhodophiala bifida bulb with potential anti-arthritic activity. In this context, we evaluated whether montanine has a disease modifying anti-rheumatic activity in two arthritis models and its effect in vitro on lymphocyte proliferation and on invasiveness of fibroblast-like synoviocytes (FLS). Antigen-induced arthritis (AIA) was performed in Balb/C mice with methylated bovine serum albumin, and nociception and leukocytes migration into the knee joint were evaluated. Collagen-induced arthritis (CIA) was performed in DBA/1J mice, and arthritis development and severity were assessed by clinical and histological scoring and articular nociception. Montanine was administered intraperitoneally twice a day. Lymphocyte proliferation stimulated by concanavalin A in 48h was performed with MTT assay, while FLS invasion in 24h was assayed in a Matrigel-coated transwell system. Administration of montanine decreased nociception (P<0.001) and leukocyte articular migration (P<0.001) in mice with AIA. In mice with CIA, treatment with montanine reduced severity of arthritis and joint damage assessed by clinical (P<0.001) and histological (P<0.05) scores and ameliorated articular nociception (P<0.05). In vitro, montanine inhibited lymphocyte proliferation stimulated with ConA (P<0.001) and decreased FLS invasion (P<0.05) by 54%, with an action independent of cytotoxicity. Our findings suggest that montanine can be further explored as an innovative pharmacological approach for autoimmune diseases such as arthritis.

Amaryllidaceae Alkaloids of Different Structural Types from Narcissus L. cv. Professor Einstein and Their Cytotoxic Activity

“…They are characterized by a 5,11-methanomorphantridine ring system, the only differencies being the substitutions and configuration at C-2 and C-3 centers (Figure 3) [40]. Some of these compounds have been screened against different cancerous cells [12,41]. Montanine and manthine showed strong in vitro growth inhibitory effect on three apoptosisresistant cancer cell lines (A549, SKMEL-29, and U373) and three apoptosis-sensitive cancer cell lines (MCF7, Hs683, and B16F10) with IC50 values between 5 and 31 µM [12].…”

Alkaloids of Phaedranassa dubia (Kunth) J.F. Macbr. and Phaedranassa brevifolia Meerow (Amaryllidaceae) from Ecuador and its cholinesterase-inhibitory activity

“…Lycorine ( 5 ), galanthamine ( 9 ) and pancratinine C ( 11 ) (6.21, 3.36 and 8.11 mg GAL.g −1 AE, respectively) also have been identified in the alkaloid extract of P. brevifolia by GC-MS ( Table 1 ). The compound pancratinine C ( 11 ) belongs to the montanine-type alkaloids, which have interesting biological proprieties, such as anxiolytic, anti-depressive, anticonvulsive, antitumoral and anti-inflammatory effects ( Da Silva et al., 2006 ; Cedrón et al., 2015 ; Farinon et al., 2017 ; Govindaraju et al., 2018 ).…”

Therapeutic potential of alkaloids in autoimmune diseases: Promising candidates for clinical trials

“…Rhodophiala bifida bulb led to the isolation of an alkaloid montanine, which exhibited significant anti‐arthritic action in animal models (Farinon et al, 2017). Also, the effects of the compound on disease modification, lymphocyte proliferation and invasiveness of fibroblast‐like synoviocytes were assessed and overall positive effects were found.…”

“…Positive effects of the compound on disease modification, lymphocyte proliferation and invasiveness of fibroblastlike synoviocytes were noted. (Farinon et al, 2017) In vitro (isolated fibroblastslike synoviocytes).…”